Background
While pain is a common feature following musculoskeletal (MSK) trauma, the phenomenon is complex, and the experience is unique to each patient. While previous models characterize pain as the direct result of tissue damage, newer models endorse multifaceted drivers recognizing the pain experience as highly subjective and influenced by interactions of biology, psychology and social influences [
1]. Inconsistent relationships between clinical pain outcomes and key physiological mechanisms [
2] has made management of post-trauma pain and interference difficult. Chronic pain is recognized as a distinct pathological condition [
3] that disrupts daily life [
4]. The incidence and prevalence of chronic pain is estimated to be nearly 20% of adults in Canada [
5] and the United States [
6] with large economic and social burden [
7].
The inability to consistently predict or prevent the transition from acute-to-chronic is partially related to the lack of clear understanding of the mechanisms involved [
8]. In addition, many prior longitudinal studies have evaluated outcomes and differences at specific time-points rather than actual trajectories. As a result, clinicians are often left to adopt a ‘wait and see’ approach to identify those patients who are not recovering, though by the time such a case arises it is too late to prevent persistent problems. We and others in the field suggest that better mechanism-based prognostic models are needed to accurately and consistently identify those at greatest risk of transitioning from acute to chronic pain [
9,
10]. In this way, more targeted interventions to mitigate risk and improve distal outcomes may be attempted.
Pain prognosis as a field of study has evolved considerably over the past two decades, with emphasis added in areas such as acute whiplash-associated disorder [
11] and acute low back pain [
12]. However, considerable challenges persist, including i) the nature and importance of the outcomes being predicted and ii) the multitude of confounding factors influencing the value prognostic models [
13]. Traditionally, pain intensity (or severity) has been the most common outcome predicted in prognostic MSK trauma research, and acute pain intensity has been a consistent predictor of those outcomes [
14,
15]. For example, Panken and colleagues [
16] conducted growth mixture modeling (GMM) to identify 3 trajectories that best described the trajectory of pain intensity in 622 participants with low back pain of median 5.8 weeks duration (2 to 780 weeks). Their results showed three distinct categories of recovery wherein people either had consistently low pain, consistently high pain, or showed a gradual recovery over a period of 12 months. This type of 3-class trajectory model appears to be showing consistency across other traumatic injuries, such as whiplash [
17]. Outstanding questions persist including the translation of these findings to injuries affecting other parts of the body, and how choice of outcome may affect these. A better understanding of recovery trajectories will inform prognostic assessment of patients, regardless of the trauma or diagnosis. These recovery trajectories may also help to direct healthcare and theranostic (individualized treatment) resources to those who would benefit most, while reducing wasted resources for those quick to recover.
The purpose of this study was to investigate the trajectories in pain and functional interference following non-catastrophic MSK trauma in a mixed sample of both axial and peripheral non-catastrophic trauma drawn from two different countries. This was conceptualized as a first step towards a non-body-region-specific approach to prognostic clinical phenotyping of people with acute, non-catastrophic MSK trauma.
Discussion
This study has defined anticipated recovery trajectories following non-catastrophic MSK trauma in mixed geographic and body region samples. The models were created using a mixed sample of working-age adults across two different institutions, in two different countries, with injuries affecting different body regions. GMM adequately identified three trajectories of pain-related interference and two trajectories for pain severity in adult participants followed for up to 52 weeks after non-catastrophic MSK trauma. These trajectories have been labeled based on their intercept, slope, and quadratic function for use in future prognostic phenotyping work.
The trajectories for functional interference are like those derived by other authors in region-specific samples, though potentially important differences may exist. For example, Sterling and colleagues [
17] identified three curvilinear classes of recovery from traumatic neck pain that could be discriminated by baseline (y-intercept) disability scores. In contrast, our model has identified a ‘Delayed Recovery’ group that entered the study with high functional interference not different from the
Minimal or No Recovery class but had recovered by the final 12-month follow-up. Our model is more similar to that of Panken and colleagues [
16] who also identified a ‘Delayed Recovery’ class in a sample of adults with low back pain, though the outcome was pain severity rather than functional interference. The middle trajectory casts some doubt on previous findings, including our own prior meta-analysis [
40], suggesting that those likely to develop chronic problems can be reliably identified with higher baseline interference or pain scores. In the current analysis, those in the delayed interference recovery group would be misclassified based on baseline interference scores alone. Risk phenotyping for this group will require further exploration in future studies. This work does lend support to the notion that those who enter a longitudinal study with lower pain or interference scores are less likely to report persistent problems, and this appears to be independent of body region.
The identification of a trajectory representing over 41% of the sample that shows little or no improvement in functional scores over all time-points is concerning. However, these results are consistent with prior primary and secondary evidence that indicates approximately 50% of people following acute neck or low back injuries do not fully recover [
41]. The proportion of participants in this trajectory is nearly identical to that identified by Panken and colleagues (45.2% of their sample) [
16]. The Rapid Recovery group, representing 32.0% of the sample, has also been consistently identified in both neck [
17,
42] and low back pain [
43]. Despite some differences in shape, the 3-trajectory model has now been identified with striking consistency across clinical populations worldwide. This includes trajectories of pain and disability in a large population-level study of people with chronic pain in Canada [
44], and post-operative pain in Belgium and the United States [
45,
46]. Even in studies that have identified more trajectories in hip (Netherlands) [
47] and low back pain (UK) [
48], the existence of three stable classes represent the highest proportions with other smaller classes representing participants with fluctuating symptoms. Our a priori criterion of rejecting class structures with fewer than 10% of the sample may have masked some of these smaller groups with irregular symptoms. That said, these smaller classes may yet emerge with larger samples though we suggest that the field move with more vigor towards predicting and defining those in each individual trajectory.
Pain Severity as an outcome favoured a 2-class model. Contrary to the functional interference findings, the largest proportion for pain severity was the rapid recovery trajectory. We considered endorsing a 3-class model for consistency with interference to facilitate clinical translation. However, a third ‘moderate persistent symptoms’ trajectory could be identified using a base (unadjusted) model but included only 8.3% of the sample and was therefore rejected. Again, our trajectories appear like those of prior research. Downie and colleagues [
43] followed a sample of participants with acute low back pain for 12 weeks and also identified 70.1% that showed rapid recovery. The difference in proportions between the outcomes highlights that pain severity and functional interference, while related, are distinct constructs that warrant separate investigation and may lead to different recovery status. The 2-trajectory model for Severity fits with prior work indicating that persistent pain symptoms can be predicted by pain severity at baseline [
15], and that approximately 15–20% of the North American adult population will report daily chronic pain [
5,
6].
The person-level variables that best predicted
Minimal or No Recovery class membership are potentially useful for future study design. Prior work has shown that females [
40] and older participants [
49] are at greater risk of poor outcomes following acute neck trauma. In our sample, the odds of being in the poor interference trajectory was also approximately 2.4x greater for females than males, while age did not predict class membership for either outcome. The strongest predictor of class membership regardless of outcome however was region of injury. Those who endorsed neck or low back injuries were 23x more likely to be assigned to the poor interference trajectory and 7x more likely to be assigned to the higher pain outcome group. These results are generally in keeping with prior work showing that patients who have experienced non-catastrophic axial traumas tend to rate symptoms as more severe and more distressing than those with non-catastrophic traumas involving the extremities [
50]. These results would also seem to indicate that clinicians and researchers might expect a greater proportion of poor outcomes in females reporting neck or back injuries.
A clinical summary of this work suggests that unlike what has been described in previous literature, initial symptom severity alone may not be adequate to predict long-term outcomes. Although people who rapidly recover will likely have lower levels of initial severity or disability, it is still possible to experience a full recovery despite high baseline symptoms. These individuals (as indicated by the “delayed recovery trajectory”) may recover at a slower rate, but still be fully functional by 12 months. It is not entirely clear which factors will distinguish between delayed and minimal recovery, but the data suggests that significant improvements in interference can occur by 1–3 months for those in the delayed trajectory. Close monitoring of functional status along with physical and psychosocial variables such as pre-existing psychological/pain conditions, employment status, sex, and location of trauma in the initial 3 months will be relevant for interdisciplinary treatment and the potential for early intervention. Identifying and addressing these elements as soon as possible may prevent a minimal recovery scenario.
There also appears to be more variability in pain interference compared to severity as recovery tends to occur in three (as opposed to two) different trajectories. This suggests that there may be more change associated with functional ability over the course of rehabilitation even if symptom severity remains relatively stable. Thus, physical rehabilitation may improve patient engagement by shifting the focus from symptom-related outcomes to achieving functional milestones throughout the course of treatment as this appears to be more amenable to change. These findings could provide a critical foothold in the rehabilitation process as it may influence individual expectations for recovery. Expectation management plays an essential role in determining the outcomes of MSK pain and may be more influential than specific treatments themselves [
51].
Another important clinical dimension to address is the influence of ethnicity. While many of the participants did not report their ethnic group, the majority of those that did identified as Caucasian (16 out of the 19% of respondents). This made it impossible to stratify the data based on ethnicity. This has important consequences for the clinical use of this study as the results may not accurately represent the general population. In a recent review [
52] investigating various dimensions of pain between ethnic groups, it was found that African-Americans tend to use more emotion-focused coping strategies compared to Caucasians. The same study also revealed some interesting differences between the US and other countries. Compared to the American population, people from Singapore seem to have a less disabling perception of pain as they rely on a more biomedical understanding of the experience. In terms of coping strategies, people from Portugal tend to use more exercise/task-oriented strategies compared to the average American.
In a qualitative study involving a multi-ethnic sample of American college students [
53], it was noted that Caucasian and African American students were more likely to define pain as a negative experience compared to Asian and Hispanic students. It was also noted that cultural display rules played a role in how likely students were to express their pain to others. African American and Hispanic students felt more comfortable expressing their pain, whereas Caucasian and Asian students reported being less likely to express their pain for reasons related to stigma and embarrassment. These studies illustrate the influence of both race and ethnicity in the overall experience of pain, which would likely influence their recovery trajectory following a traumatic injury. Since many participants in our study did not report their ethnicity, we are unable to draw any legitimate conclusions about the differences between ethnic groups. Between the US and Canada, the Chicago cohort displayed a greater proportion of participants in the poor outcome groups. However, this may just be a consequence of many other factors including the location of injury rather than any sociocultural differences between the two countries.
Limitations
The most notable risk of potential confounding in this study is the combination of two separate databases from two different countries. The participants were not matched, but both studies had very similar inclusion and exclusion criteria. While the important aspects of data collection were consistent across the two cohorts, there were obvious differences. One is the medicolegal context between the private payer system in the United States and the socialized health system in Canada. There has yet to be any compelling evidence to suggest that the rate or amount of improvement in these common MSK traumas is different between the two neighboring countries. However we acknowledge that work in other countries with less established personal injury insurance systems (e.g. Lithuania [
54,
55], Greece [
55,
56]) have been previously associated with different rates of chronic post-trauma neck pain compared to other western countries. Dedicated international research collaborations with standardized case definitions and outcomes are required to more fully explore the effect of personal injury insurance claims. As mentioned previously, another limitation is the paucity of data concerning ethnicity in both cohorts. Identifying meaningful patterns in the cohorts together speaks to the potential generalizability of the findings, but stratification by ethnicity would have provided key insights into the potential differences among ethnic groups. This is definitely an area for future study as it would contribute significantly to our understanding of prognosis in different populations.
The two cohorts also used different standardized patient reported outcomes for measuring functional interference, with the Chicago cohort using the NDI and the London cohort using the BPI. The two scales have never been directly compared for equality of measurement properties, though each have been independently explored against other standardized tools and shown to have similar associations [
18,
19,
23,
24]. Both share two nearly identical items (sleep, work) and also include items pertaining to activity and recreation. The BPI is intended as a more generic tool, including walking, which is less relevant to those reporting neck pain only. Although we could not standardize the tools used in each database after the fact, we are confident that converting each to a percent of total scale score ensures similar constructs of “functional interference” and justifies combining the two databases for analysis. Importantly, there was no significant difference in baseline % Interference scores between the two cohorts (not shown). In addition, the inclusion of ‘region’ as a covariate in the models provided some protection against spurious findings, as the majority of those in the database with neck trauma came from the Chicago cohort. There exists a reciprocal tension between internal and external validity, and we have chosen to favor the latter through the inclusion of mixed samples, countries, and outcomes. Nevertheless, we acknowledge the effect on internal validity in doing so. It is also worth noting that the use of different, region-specific pain scales is typical within a clinical setting as functional outcomes are often tied to region-specific limitations. We have attempted to reduce these differences by ensuring that the core constructs of severity and interference were captured to some degree in both cohorts.
Another potential limitation is the sample size of the present study, although 205 is not considered small by LGCA standards. Some research groups have identified smaller trajectory classes hidden within larger samples (though these tend to represent 10% or less of the overall proportion), while other large scale analyses have similarly reported three trajectories [
16,
44]. While it is possible that other trajectories comprised of smaller proportions exist in our data but were not identified, we propose that these would be rare enough to not substantively affect prognosis or treatment decisions. Finally, the use of the quadratic term made clinical and statistical sense, though a purely linear model could be identified that resulted in similar class structures with some differences in proportions assigned to each. The posterior validation steps in this study were undertaken to strengthen our confidence in the results of the quadratic models. These steps provided the added advantage of better prediction for missing data and a clear indication of recovery in the rapid class by 3-month follow-up after which the curve flattened considerably.
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